(a) Field of Invention
This invention relates to a method for lowering blood glucose levels in a mammal suffering from diabetes mellitus. More particularly, it pertains to a method for diabetic control of a subject by administering 1,3-dioxo-1H-benz[de]isoquinoline-2(3H)-acetic acid.
(b) Prior Art
For many years diabetes mellitus has been treated with drugs by two established methods, one by administering insulin and the other by administering oral hypoglycemic agents. These methods have benefited hundreds of thousands of diabetics by improving their well-being and prolonging their lives. However, both of these methods have been used with certain reservations. Treatment with insulin requires ordinarily that the diabetic self adminster injections of insulin on a daily basis. This practice introduces the hazards of improper measurements and non-septic injection techniques aside from the grave disadvantage of repeated injections. In addition, continued daily injections of insulin can lead to an immune response to insulin. The use of the presently available oral diabetic agents also has been associated with reservations. Although these agents, for example, tolbutamide, tolazamide, acetohexamide, chlorpropamide and phenformin, can be used effectively for treating diabetes mellitus in most cases, the continued use of these agents has been associated with a significant incidence of serious side effects such as to warrant cautious use of these agents; for example, see S. A. Hagg in "Drug Therapy Reviews," Vol. 1, R. R. Miller and D. J. Greenblatt, Ed., Masson Publishing U.S.A., Inc., New York, Paris, Barcelona and Milan, 1977, p. 277. In addition, the oral hypoglycemic agents can be used only for the treatment of maturity-onset diabetes wherein the diabetic has some insulin secreting pancreatic beta cells.
Accordingly, there is a need for a therapeutic method for treating diabetes mellitus which is safe, reliable and which can be administered conveniently.
Surprisingly, I have now found that 1,3-dioxo-1H-benz[de]isoquinoline-2(3H)-acetic acid, or a therapeutically acceptable salt thereof, is an effective hypoglycemic agent when administered to diabetic humans and animals. This finding, coupled with the fact that this agent is a relatively safe drug, renders the method of this invention particularly useful and advantageous.
The active agent of this invention, 1,3-dioxo-1H-benz[de]isoquinoline-2(3H)-acetic acid, or a therapeutically acceptable salt thereof, is disclosed in U.S. Pat. No. 3,821,385, issued June 28, 1974. This active agent, hereinafter sometimes designated as "alrestatin," previously has been reported to be an inhibitor of the enzyme aldose reductase, and to be useful in preventing or relieving diabetic complications such as cataracts, neuropathy, nephropathy and retinopathy (see U.S. Pat. No. 3,821,383, cited above).